title: Genetic evaluation of short stature.
abstract: After a proper medical history, growth analysis and physical examination of a short child, followed by radiological and laboratory screening, the clinician may decide to perform genetic testing. We propose several clinical algorithms that can be used to establish the diagnosis. GH1 and GHRHR should be tested in children with severe isolated growth hormone deficiency and a positive family history. A multiple pituitary dysfunction can be caused by defects in several genes, of which PROP1 and POU1F1 are most common. GH resistance can be caused by genetic defects in GHR, STAT5B, IGF1, IGFALS, which all have their specific clinical and biochemical characteristics. IGF-I resistance is seen in heterozygous defects of the IGF1R. If besides short stature additional abnormalities are present, these should be matched with known dysmorphic syndromes. If no obvious candidate gene can be determined, a whole genome approach can be taken to check for deletions, duplications and/or uniparental disomies.
authors.affiliation: Department of Paediatrics, J6S Leiden University Medical Center, Leiden, The Netherlands. j.m.wit@lumc.nl
authors.forename: J M
authors.initials: JM
authors.lastname: Wit
authors.forename: W
authors.initials: W
authors.lastname: Kiess
authors.forename: P
authors.initials: P
authors.lastname: Mullis
mesh_terms: D000465:Algorithms; D001827:Body Height / Q000235:genetics; D002648:Child; D005820:Genetic Testing; D006130:Growth Disorders / Q000235:genetics*; D019382:Human Growth Hormone / Q000172:deficiency / Q000235:genetics; D006801:Humans; D017526:Receptor, IGF Type 1 / Q000235:genetics; D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D050799:STAT5 Transcription Factor / Q000235:genetics
chemical_list: D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D050799:STAT5 Transcription Factor; C494095:STAT5B protein, human; D019382:Human Growth Hormone; D017526:Receptor, IGF Type 1; C048250:somatotropin releasing hormone receptor